GROMACS version: 2023.2
GROMACS modification: No
I am trying to measure the change in free energy of a protein between two solvents, water and a silicon based oil. The system is equilibrated with the protein initially in the water with the solvents separated and the goal is to pull the protein through the water and into the oil. The pull code I am using is as follows:
; Pull settings
pull = yes
pull-ncoords = 1
pull-ngroups = 1
pull-group1-name = Protein ; Which index group is being pulled
pull-coord1-type = umbrella ; Harmonic potential, changes with distance
pull-coord1-geometry = distance ; Pulling is applied along x direction against a point
pull-coord1-groups = 0 1 ; Which groups will be pulled, 0=point reference, 1=Protein
pull-coord1-dim = Y N N ; Apply pulling along x direction only
pull-coord1-origin = 10.89 4.00 3.28 ; Protein COM, reference point to pull against
pull-coord1-start = yes ; Add COM distance to the reference distance
pull-coord1-rate = 0.001 ; (nm/ps)
pull-coord1-k = 1000 ; (kJ mol^-1 nm^-2) harmonic pulling force constant
The goal is to pull the protein from the water into the oil, select windows for sampling and perform NPT equilibration for each of these windows and then a longer production simulation for each window. Then use umbrella sampling to measure the change in energy between the solvents, as well as at the interface.
My question is with regards to using an absolute reference point and the warning that comes with it:
WARNING 1 [file pull_grompp.mdp]:
You are using an absolute reference for pulling, but the rest of the
system does not have an absolute reference. This will lead to artifacts.
I have tested using the water and oil as a second reference group with both distance and cylindrical geometry settings and these lead to really unphysical behaviours as the solvents positions are not restrained. Unlike in a lipid bilayer system or protein-ligand system I do not have a second restrained group to pull against.
I am wondering if there is another way I should do this or if there is anything I am missing. I understand that in general it is not a good idea to ignore these warnings. However, I am not sure how else to proceed.
Thanks!